EEG mapping of left hemisphere dysfunction during motor performance in schizophrenia.

With a newly developed system of brain electrical activity mapping we studied 10 right-handed, neuroleptic-treated schizophrenics (five of the disorganized, five of the paranoid type, corresponding to 295.1 and .3 in DSM-III), compared with 10 normal controls. Increasingly complex motor tasks were used for cortical activation, all functional states being referenced to resting states recorded after a special relaxation program. We found higher delta and theta amplitudes during rest, as noted in previous studies, and lower beta power values. As a major result, however, we found a widespread left hemisphere dysfunction in schizophrenics, predominantly in the left primary sensory and motor areas. Additionally, we found signs of a "compensatory" overactivation in patients in motor tasks, when this hemisphere is not "used" by normal persons. The results support our findings obtained with this method during multisensory motor coordination in schizophrenia. The results in these patients suggest that these are not merely vigilance, attention, or motivation dysfunctions, but rather specific cortical correlates of impaired motor performance.

Bilateral brain dysfunction during motor activation in type II schizophrenia measured by EEG mapping.

In this final electroencephalographic (EEG) mapping study of our series on motor dysfunction in neuroleptic-treated schizophrenic patients, we studied 10 right-handed patients with marked negative symptomatology [type II; raw score on the SANS (Munich version) 31.4 +/- 5.1]. Simple and multisensorimotor tasks involving both the dominant and nondominant hand were used for cortical activation. All tasks were referred to resting states obtained after specially designed relaxation procedures. In contrast to predominantly type I patients (SANS-MV score 12.3 +/- 4.9) of our previous EEG mapping studies, we found for resting states minor evidence (only) of increased power values in the frequency bands delta and theta. Furthermore, in contrast to signs of "left hemisphere dysfunction" and possible "compensatory right hemisphere overactivation" during motor tasks, which we discussed previously for our type I patients, we found for the type II schizophrenics a bilateral brain dysfunction. This consisted of "nonreactivity" in all frequency bands except alpha, in which, on the contrary, a "hyperreactivity" seemed to be present. In combination with evidence of bilateral hemispheric dysfunction in type II patients reported by other authors using EEG, evoked potentials, regional cerebral blood flow (rCBF) and magnetic resonance imaging (MRI) methods, this suggests that marked bilateral brain dysfunction may be correlated in schizophrenia with a clinical syndrome corresponding rather to the "negative pole" of the positive-negative dimension. In contrast, "left hemisphere dysfunction" and "signs of compensatory overactivation" seem to be linked more to a "positive" symptomatology. Finally, discrepancies of our EEG mapping and rCBF findings during motor activity suggest, speculatively, "uncoupling" between electrical and circulatory parameters in schizophrenia involving both hemispheres in type II, and predominantly the left hemisphere in type I, patients.

Effect of controlled-release carbidopa/levodopa on motor performance in advanced Parkinson's disease.

Twenty parkinsonian patients were treated with controlled-release carbidopa/levodopa (Sinemet CR). All were affected by therapeutic response fluctuations related to the timing of drug administration. The daily dosage after 1 year, 766 mg +/- 250 mg, was increased by 23% compared with standard Sinemet dosage, without additional secondary effects. Parkinsonian scores improved by 43%; the prolongation of "on" periods was 63%. Nevertheless, 7 patients withdrew from this study during the 1st month of treatment. Only 1 withdrew due to an adverse reaction to the formulation, a recurrence of hallucinations. The progressive effect of the 1st morning dose and the often unpredictable time at which the product first takes effect were found to be frustrating for the other patients who withdrew. We believe that this disappointment can be avoided by giving new patients the controlled-release formulation from the start of therapy.

Botulinum antibodies in dystonic patients treated with type A botulinum toxin: frequency and significance.

We measured serum antibodies to botulinum toxin (ABT) in 96 patients with focal dystonia who had been treated with type A botulinum toxin. The frequency of detectable ABT was 3% (three patients). Patients with ABT had received more than 50 ng of botulinum toxin, and the shortest time between two injections was significantly less than in patients without ABT. The clinical evolution of the three patients was heterogeneous: one had decreased effectiveness with repeated injections, another had persistent improvement, and the third never responded to toxin injections.

A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.

We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G533-->A mutation and for a new mutation, G1171-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene. Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM2 gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate.

Auditory perception of music measured by brain electrical activity mapping.

The brain electrical activity of right-handed normal subjects was studied while they were exposed to auditory stimulation of the music type. The material presented was a note, a scale and a melody, recorded on magnetic tape. Each stimulus condition lasted 45 sec. The first 30 sec were analysed using brain electrical activity mapping in the delta (1-4 Hz), alpha (8-12 Hz) and beta 2 (18-24 Hz) frequency bands. The results showed significant bilateral reaction differences for all conditions, showing a left midtemporal activation predominance for the note and scale conditions, but a right midtemporal and frontal predominance for the melody. The results are discussed in terms of functional specialization for different levels of processing.

Somatostatin-like immunoreactivity and acetylcholinesterase activities in cerebrospinal fluid of patients with Alzheimer disease and senile dementia of the Alzheimer type.

Somatostatin-like immunoreactivity (SLI) and acetylcholinesterase (AchE) activities were measured in the cerebrospinal fluid of 25 patients with senile dementia of the Alzheimer type (SDAT). Both SLI levels and AchE activities were reduced in the CSF of SDAT patients. The SLI levels and AchE activities were not correlated with the duration and the dementia score. However, in two patients the CSF SLI concentration was in agreement with the SLI levels in the frontal cortex obtained by biopsy. Our findings suggest that CSF SLI may be a good index of cortical SLI activities.

Motor responses measured by brain electrical activity mapping.

The brain electrical activity of right-handed normal subjects was studied while they were exposed to motor performance tasks that were of increasing difficulty. Each task lasted 45-60 s, and a 30-s period of each task was analyzed by a spectrum analyzer. Data are presented in topographic maps showing the electrical activity for each task, in delta (1-4 cycles [c]/s), alpha (8-12 c/s), and beta 2 (18-24 c/s). The results showed a bilateral decrease in amplitude in sensorimotor areas relative to baseline, for a single hand movement. Tasks that required the programming of movement showed baseline/task differences in amplitude in additional areas; the right frontal area, the prefrontal area, the posterior parietal area, and the left temporal area. The results obtained suggest that different topographical areas are involved in motor tasks that require increased level of programming.

The shadow of movement.

Movement is preceded, accompanied and followed by reactions which give to the primary action its correct execution and ensure that the body's axis, together with the limbs, maintains the right balance. If these reactions are interfered with, incoordination of movement, lack of balance, hypertonia or dystonia may all appear. In the case of dystonia, postural mechanisms tend to become dominant and take over from the kinetic component of movement. In the upper limbs, the dystonic posture follows patterns analogous to those used by monkeys for postural purposes. Thus, while the initial mechanisms of movement represent highly sophisticated processes thoroughly adapted to living in an upright state, the reactions that go with the movement are more primitive and probably have a less helpful role.

Activity and acceptability of piribedil in Parkinson's disease: a multicentre study.

Several controlled trials have shown that the dopamine agonist, Trivastal (piribedil), is active in the treatment of Parkinson's disease, particularly with regard to tremor. To determine its efficacy as monotherapy in patients previously untreated with levodopa, a 3-month multicentre study was conducted with Trivastal 50 mg LP in 113 patients with idiopathic Parkinson's disease. The study population consisted of 66 men and 47 women, aged 63.1, SD 0.6 (43-79) years with a 2.1, SD 0.2 (1-15) year history of Parkinson's disease. Mean disease stage was 1.82 (1-4) by the Hoehn and Yahr classification. Tremor was the predominant clinical feature in 42 patients; the remaining 71 patients displayed the full parkinsonian syndrom. Trivastal 50 mg LP was prescribed stepwise up to doses of 150-250 (207, SD 6.4) mg/day at the end of 3 months. No concomitant anti-parkinsonian medication was given. Patients were clinically assessed at 1, 2 and 3 months on the Webster scale, a specific tremor scale and the HARD depression scale. Mean results were as follows in the 90 patients completing the study. On the Webster scale, tremor fell from 1.7 to 1 (-41%, P less than 0.001), bradykinesia from 1.5 to 0.8 (-47%, P less than 0.001) and rigidity from 1.3 to 0.9 (-31%, P less than 0.001); on the specific scale, rest tremor decreased in daily duration and amplitude from 3.9 to 2.4 (-39%, P less than 0.001) and from 2.9 to 2.1 (-35%, P less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Menzel's hereditary ataxia with slow eye movements and myoclonus. A clinico-pathological study.

The patient we describe had cerebellar ataxia, slow eye movements, myoclonus, facial dystonia and signs of spinal cord and peripheral nerve involvement. The patient's mother, brother and sister died from the same disease. Neuropathological examination revealed lesions of olivo-ponto-cerebellar atrophy (OPCA) associated with spinal cord degenerative changes characteristic of Menzel's hereditary ataxia. Although myoclonus was similar to Hunt's dyssynergia cerebellaris myonica, pathological findings did not show significant involvement of the dentate nucleus or superior cerebellar peduncle and physiopathological hypotheses for myoclonus are discussed. Slow eye movement is emphasized in the propositus and we suggest that it could be specific of one type of OPCA. Its pathological significance is discussed, but a primitive and unique involvement of the paramedian pontine reticular formation is unlikely.

Loss of topographic memory with learning deficits.

A case is reported in which a patient with a vascular accident involving the posterior portion of the minor hemisphere presented a topographic memory loss and also deficits in his ability to learn certain types of new material. The study of this case has led us to re-examine spatial functioning in light of both human and animal research. Based on clinical and experimental evidence we have proposed that a unitary interpretation can account for the various spatial deficits associated with posterior righ hemisphere lesions. We have also suggested that the establishment of a spatial map for orientation probably depends not only on posterior right hemisphere structures but also may require the participation of structures which are more specifically concerned with learning and memory, such as the hippocampus or at least the connections between the hippocampus and these structures.

Dystonia--L-dopa responsive or juvenile parkinsonism?

Four cases of dystonia occurring in two families are reported. The first symptoms consisting of dystonia and rigidity appeared early in childhood, in the first months in one family and of ages two and five years respectively in the other. In two cases, transient tremor was noted. These four children have been treated with L-dopa with prompt spectacular results, in cases 1 and 2, with more gradual less complete results in the others. L-dopa treatment was continued twelve, eleven, six, and five years, respectively, without any developmental problems. Motor function remains satisfactory and school work is normal. The only secondary effect observed was the occurrence of dyskinesia. The relation between L-dopa responsive dystonia and Parkinson's disease is discussed.

Patients with Alzheimer's disease show an increased content of 15 Kdalton somatostatin precursor and a lowered level of tetradecapeptide in their cerebrospinal fluid.

The relative proportions of both somatostatin-14 and its precursors somatostatin-28 and the 15 Kdalton prosomatostatin were evaluated by radioimmunoassay in the cerebrospinal fluid of patients with Alzheimer's disease. It was observed that the patients have a lowered content in the tetradecapeptide somatostatin while they exhibit a significant increase in unprocessed 15 Kda precursor. These results indicate that these patients possess impaired processing mechanisms which may be responsible for the lowered content in mature somatostatin-14. These observations may provide a valuable test for the ante-mortem diagnosis of the disease. They are discussed in connection with others suggesting that Alzheimer's patients may be selectively altered in their somatostatinergic neurones of their cerebral cortex (Morrison et al. (1985) Nature 314, 90-92. Roberts et al. (1985) Nature 314, 92-94).

Chronic administration of L-dopa affects the movement-related cortical potentials of patients with Parkinson's disease.

The chronic effect of L-Dopa administration on the movement-related cortical potentials (MRCPs) was studied in two groups of patients with Parkinson's disease (PD): patients de novo (DN) and patients with on-off fluctuations. The BP and NS' premovement components of MRCPs associated with wrist flexion were assessed by their gradients and by their distribution on the midline (CZ) and the ipsilateral and contralateral hand sensorimotor areas. The treatment efficacy was controlled by a decrease in PD score (Columbia University Rating Scale). The BP component was absent in four out of nine patients DN. After 3 months of treatment, BP and NS' were recorded in six out of seven patients, and the NS' slope was significantly increased in all patients. In the off phase, MRCPs from patients with on-off fluctuations did not present a BP component. In the on phase, the NS' slope was increased and the BP was recorded in two out of nine patients. These patients exhibited an earlier PD stage (Hoehn and Yahr, stage 3). These two patterns of changes in the MRCPs induced by L-Dopa treatment suggest that the BP component was recorded in patients DN when a partial resolution of the nigrostriatal activity could occur. In patients with severe fluctuations, the dopaminergic striatal pathway was more severely affected and the increase of the NS' component demonstrated the activation of extrastriatal dopamine sites within the central nervous system (limbic and cortical structures, in particular).

Therapeutic response to progabide in neuroleptic- and L-dopa-induced dyskinesias.

The results of two trials conducted in human dyskinesia with progabide, a specific gamma-aminobutyric acid (GABA) receptor agonist, are reviewed. In one trial, 13 parkinsonian patients with L-DOPA-induced dyskinesia (LDD) and "on-off" fluctuations were included in a double-blind controlled trial progabide versus placebo. No change was observed during this trial in the severity of dyskinesia on progabide treatment but the drug significantly extended the "on" period as compared with placebo. In the second trial, 20 patients with neuroleptic-induced dyskinesia (TD) entered an open dose ranging trial with progabide. Fourteen of the 16 patients who completed the trial had a good-to-excellent therapeutic response. According to these results, progabide does not seem to have the same therapeutic benefit in LDD as TD. These data suggest that the hypothesis of a dopaminergic supersensitivity as a similar pathogenic substrate for both clinical conditions should be reconsidered. If this hypothesis remains the most consistent to explain the occurrence of LDD, the therapeutic effect of progabide in TD is an argument for an implication of the GABAergic system in the appearance of TD.

Postural adjustments associated with rapid voluntary arm movements in patients with Parkinson's disease.

To determine the extent to which deficits in coordination between posture and movement are influenced by postural disorders, postural adjustments associated with rapid voluntary arm movement were studied in PD patients and controls. EMG activity in postural muscles of the lower limbs and the trunk and local anteroposterior accelerations of the upper part of the leg were recorded in subjects who rapidly raised their arms to a horizontal position in response to a visual signal. The arm movement was characterized electromyographically by EMG activity from the deltoid muscle (anterior portion) and kinetically by acceleration of the arm. Study of characteristics of voluntary movement showed a nonsignificant increase in RT (simple-reaction time task) and an important increase in MT. There were important differences between PD patients and control subjects with regard to postural adjustments. Timing between voluntary movement and postural movement was anticipatory in 5% of PD patients, whereas it was anticipatory in 100% of control subjects. In PD patients, organization of early postural adjustments was not specific to voluntary movement; in control subjects, organization of early postural adjustments was specific to the forthcoming movement. Last, a possible functional relation between the "quality" of postural adjustments and a reduction in motor performance of normal subjects is suggested.

Spasmodic torticollis--review of 220 patients.

220 patients with isolated and idiopathic spasmodic torticollis were followed and treated over a 14 year period. Each patient was given a short questionnaire leading to the present retrospective data analysis. In most areas, including female preponderance and frequency of postural tremor, the findings confirmed previous studies and highlighted particular points: importance of psychopathological antecedents and association with stressful life-events. The discussion deals with some of the conflicting debates surrounding this unusual disorder. What is the role of psychopathological factors? What is the therapeutic prognosis? The best therapeutic results were obtained by combining anticholinergic drugs, local injections and rehabilitation.

[Changes in movement-related cortical potentials in Parkinson's patients before and after treatment with levodopa]. / Evolution des potentiels corticaux liés au mouvement chez les patients parkinsoniens, avant et après traitement par la lévodopa.

Cortical potentials associated with voluntary, self-paced wrist flexion (MRPs) were recorded from 3 scalp locations (Cz and psi contralateral hand motor area) in patients with Parkinson's disease (9 de novo patients and 30 L-Dopa treated patients). The analysis concerned 3 components of the MRPs: the 2 slow negative shifts (NS1 and N1) before the movement onset and the motor potential (MP). The NSI amplitude was measured at Cz, the peak negativity N1 and MP from contralateral hand motor area location. The potential distribution was also studied. The amplitude of the MRPs components was the same as in the normals. But in de novo patients, the potential distribution of the NS1 component was different; a Cz preponderance of the NS1 amplitude was not found. In patients treated with L-Dopa, there is a negative correlation between the changes in amplitude and the changes in clinical rating for NS1, N1 and MP components. The decrease in the MRPs components was significant from stage III and IV of the Hoehn and Yahr scales. After L-Dopa therapy, the NS1 component from de novo patients was increased in amplitude. The amplitude of the MRPs components from patients with L-Dopa induced clinical fluctuations was reduced during "off" period in comparison to "on" period. The findings suggest that the NS1 potential and the N1 and MP components share 2 distinct systems for the control of voluntary movement. Their mechanism in Parkinson's disease is discussed.

[Movement-related cortical potentials in aged subjects]. / Les potentiels corticaux liés au mouvement de l'homme âgé.

Cortical potentials related to freely-executed voluntary wrist flexion (MRPs) were studied in 35 subjects aged 23-80 years. The characteristics of the MPRs in aged subjects were determined in comparison data from 14 young subjects aged 23-40 years. The analysis concerned 3 components of the MRPs: the slow negative shifts (NS1 and NS2) before the movement onset and the motor potential (MP). In the aged subject, the latencies measured at Cz show a significant lengthening of the NS1 and of the duration of NS2 (NS' of Shibasaki et al, 1980). The mean amplitude of the NS1 peak at Cz is decreased, and those of N1 (the negative peak before the movement) and MP are not significantly different from those of the young subjects. The NS2 component in the aged subject (between NS1 and N1) is thus increased. In contrast to the young subjects, who present a predominance of N1 and MP amplitudes of the contralateral motor cortex over the ipsilateral cortex, the aged subjects lose lateralization of these components. Recording of MRPs with subdural electrodes (Neshige et al, 1988) shows taht NS1 results from the activity of the supplementary motor area and from the ipsi-contralateral primary motor cortex. The increase in NS2 might be interpreted as an expression of activity coming from other structures to compensate for the reduction in NS1 in the aged subject and to maintain the level of the motor potential MP.